2,2,2-trifluoro-N-methylethanamine

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 10 g (0.1 mol) of triethylamine and 13.6 g (0.1 mol) of acetoxyacetyl chloride were added to a solution of 9.9 g (0.1 mol) of N-(2,2,2-trifluoroethyl)-N-methylamine in 150 ml of toluene and the mixture was stirred at 20° C. for 15 hours. It was then filtered and the filtrate was distilled. 17 g (79.8% of theory) of N-(2,2,2-trifluoroethyl)-N-methyl-acetoxyacetamide of boiling point 110° C./3 mbar were obtained. ##STR11## was obtained analogously; ND20 :1.4333. ##STR12## It was then filtered the filtrate was distilled

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 10 g (0.1 mol) of triethylamine and 13.6 g (0.1 mol) of acetoxyacetyl chloride were added to a solution of 9.9 g (0.1 mol) of N-(2,2,2-trifluoroethyl)-N-methylamine in 150 ml of toluene and the mixture was stirred at 20° C. for 15 hours. It was then filtered and the filtrate was distilled. 17 g (79.8% of theory) of N-(2,2,2-trifluoroethyl)-N-methyl-acetoxyacetamide of boiling point 110° C./3 mbar were obtained. ##STR11## was obtained analogously; ND20 :1.4333. ##STR12## It was then filtered the filtrate was distilled

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 10 g (0.1 mol) of triethylamine and 13.6 g (0.1 mol) of acetoxyacetyl chloride were added to a solution of 9.9 g (0.1 mol) of N-(2,2,2-trifluoroethyl)-N-methylamine in 150 ml of toluene and the mixture was stirred at 20° C. for 15 hours. It was then filtered and the filtrate was distilled. 17 g (79.8% of theory) of N-(2,2,2-trifluoroethyl)-N-methyl-acetoxyacetamide of boiling point 110° C./3 mbar were obtained. ##STR11## was obtained analogously; ND20 :1.4333. ##STR12## It was then filtered the filtrate was distilled

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a sealed reaction vessel was added cesium fluoride (0.085 g, 0.56 mmol). The reaction vessel was heated to 150° C. for 3 hours with stirring, under high vacuum. The vial was cooled to ambient temperature under high vacuum. The reaction vessel was backfilled with argon, and next was added a solution of 2,2,2-trifluoro-N-methylethanamine (purchased from Enamine) (0.019 g, 0.17 mmol) and 2-bromo-4-(5-chloropyridin-3-yl)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile (Preparative Example 3.1, 0.025 g, 0.056 mmol) in DMSO (0.30 mL). The reaction was heated to 100° C. for 12 hours. The reaction was cooled, diluted with H2O (2.0 mL) and extracted with EtOAc (2×5.0 mL). The combined organics were dried over anhydrous MgSO4, filtered and concentrated in vacuo to afford 4-(5-chloropyridin-3-yl)-2-(methyl(2,2,2-trifluoroethyl)amino)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile as a crude residue. MS ESI calc'd. for C23H24ClF3N6 [M+H]+ 477. found 477. To a sealed reaction vessel The vial was cooled to ambient temperature under high vacuum The reaction was heated to 100° C. for 12 hours The reaction was cooled extracted with EtOAc (2×5.0 mL) The combined organics were dried over anhydrous MgSO4 filtered concentrated in vacuo

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a sealed reaction vessel was added cesium fluoride (0.085 g, 0.56 mmol). The reaction vessel was heated to 150° C. for 3 hours with stirring, under high vacuum. The vial was cooled to ambient temperature under high vacuum. The reaction vessel was backfilled with argon, and next was added a solution of 2,2,2-trifluoro-N-methylethanamine (purchased from Enamine) (0.019 g, 0.17 mmol) and 2-bromo-4-(5-chloropyridin-3-yl)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile (Preparative Example 3.1, 0.025 g, 0.056 mmol) in DMSO (0.30 mL). The reaction was heated to 100° C. for 12 hours. The reaction was cooled, diluted with H2O (2.0 mL) and extracted with EtOAc (2×5.0 mL). The combined organics were dried over anhydrous MgSO4, filtered and concentrated in vacuo to afford 4-(5-chloropyridin-3-yl)-2-(methyl(2,2,2-trifluoroethyl)amino)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile as a crude residue. MS ESI calc'd. for C23H24ClF3N6 [M+H]+ 477. found 477. To a sealed reaction vessel The vial was cooled to ambient temperature under high vacuum The reaction was heated to 100° C. for 12 hours The reaction was cooled extracted with EtOAc (2×5.0 mL) The combined organics were dried over anhydrous MgSO4 filtered concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-(3-chloro-4-fluorophenylamino)-2-(pyridin-3-yl)-N-(2,2,2-trifluoroethyl)quinazoline-6-carboxamide was synthesized in a similar manner to that described for 4-(3-chloro-4-fluorophenylamino)-N-methyl-2-(pyridin-3-yl)-N-(2,2,2-trifluoroethyl)quinazoline-6-carboxamide substituting 2,2,2-trifluoroethylamine for 2,2,2-trifluoro-N-methylethylamine. The resulting product was analyzed. LCMS: r.t=1.934 min, [M+1]+=476.0. 1H-NMR (400 MHz, DMSO-d6): δ 10.43 (s, 1H), 9.54 (s, 1H), 9.32 (t, J=6.1 Hz, 1H), 9.14 (s, 1H), 8.72 (d, J=4.6 Hz, 1H), 8.68 (d, J=8.0 Hz, 1H), 8.32 (d, J=8.7 Hz, 1H), 8.27 (dd, J=6.7, 2.2 Hz, 1H), 7.98 (d, J=8.7 Hz, 1H), 7.96-7.90 (m, 1H), 7.62-7.51 (m, 2H), 4.27-4.14 (m, 2H). r.t=1.934 min, [M+1]+=476.0

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 10 g (0.1 mol) of triethylamine and 13.6 g (0.1 mol) of acetoxyacetyl chloride were added to a solution of 9.9 g (0.1 mol) of N-(2,2,2-trifluoroethyl)-N-methylamine in 150 ml of toluene and the mixture was stirred at 20° C. for 15 hours. It was then filtered and the filtrate was distilled. 17 g (79.8% of theory) of N-(2,2,2-trifluoroethyl)-N-methyl-acetoxyacetamide of boiling point 110° C./3 mbar were obtained. ##STR11## was obtained analogously; ND20 :1.4333. ##STR12## It was then filtered the filtrate was distilled